Protein kinases play critical roles in the regulation of biochemical and morphological changes associated with cellular growth and division. D'Urso et al., Science 250, 786–91, 1990; Birchmeier et al., Bioessays 15, 185–89, 1993); U.S. Pat. No. 6,200,770. They serve as growth factor receptors and signal transducers and have been implicated in cellular transformation and malignancy. Hunter et al., Cell 70, 375–87, 1992; Posada et al., Mol. Biol. Cell 3, 583–92, 1992; Hunter et al., Cell 79, 573–82, 1994. For example, protein kinases have been shown to participate in the transmission of signals from growth-factor receptors (Sturgill et al., Nature 344, 715–18, 1988; Gomez et al., Nature 353, 170–73, 1991), control of entry of cells into mitosis (Nurse et al., Nature 344, 503–08, 1990; Maller, Curr. Opin. Cell Biol. 3, 269–75, 1991), and regulation of actin bundling (Husain-Chishti et al., Nature 334, 718–21, 1988).
Protein kinases can be divided into two main groups based on either amino acid sequence similarity or specificity for either serine/threonine or tyrosine residues. A small number of dual-specificity kinases are structurally like the serine/threonine-specific group. Within the broad classification, kinases can be further sub-divided into families whose members share a higher degree of catalytic domain amino acid sequence identity and also have similar biochemical properties. Most protein kinase family members also share structural features outside the kinase domain that reflect their particular cellular roles. These include regulatory domains that control kinase activity or interaction with other proteins. Hanks et al., Science 241, 42–52, 1988).
There is a need in the art to identify protein kinase-like proteins, which can be regulated to provide therapeutic effects.